Summary It is estimated that more than 100 million people suffer from chronic pain and more than 30 million people suffer from chronic itch in the U.S. Current therapeutics for chronic pain and itch are inadequate and limited by insufficient efficacy and side effects. Although itch-sensing neurons are a subset of C-fiber nociceptors in dorsal root ganglion, pain and itch are mediated via distinct neural circuits in the spinal cord. There is also crosstalk between pain and itch pathways: pain suppresses itch while analgesic such as morphine can provoke itch. Therefore it will be of great importance to develop new drugs that can target both pain and itch. Toward this goal, we have come up with a novel strategy of developing monoclonal antibodies to treat pain and itch simultaneously. We will employ a multidisciplinary approach that combines molecular biology, biochemistry, electrophysiology in isolated cells, whole DRG preparation, and spinal cord slices, and behavioral testing of pain and itch using evoked and spontaneous responses. Successful accomplishment of the project will not only provide a better understanding of the molecular and synaptic mechanisms of pain and itch sensations but also lead to new therapies for treating debilitating pain and itch conditions.